Investigation of the Efficacy of Acamprosate and Calcium in Comparison to Placebo as Validation of a Behavioural Test for Alcohol Dependence

NCT03634917 | Completed Phase 3 DMC

• 1 other identifier: TUD-TEMACA-069
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 1

Brief Summary

Validation of a Test System to develop new medications for alcoholism (TEMA) The 'TEMA', a progressive-work alcohol self-administration paradigm, can be validated by reproducing the effect of Acamprosate and prove the effect of Calcium to reduce motivation to work for alcohol after 14 - 19 days of treatment during a period of 15 - 20 days of alcohol abstinence in a randomized, double-blind, placebo-controlled three-arm parallel-group design.

Conditions

Alcoholism

Keywords

Acamprosate; Calcium; alcohol self-administration

Outcome Measures

Primary Outcomes (1)

• Difference between cumulative CAT trials for alcohol on 1st alcohol self-administration (ASA) day and 2nd ASA day

  Each alcohol request requires prior work according to a progressive schedule (i.e., runs of the constant attention task) to earn the next alcohol infusion. Primary outcome measure is the difference in the cumulative number of work sets for alcohol in the "constant attention task" (CAT) between first alcohol self-administration day (baseline, without medication, visit 2) and the second alcohol self-administration day (after 14-19 days medication, visit 5). Comparison between: 1. Acamprosate and Placebo and 2. Calcium Carbonate and Placebo

  18 to 31 days between 1st and 2nd measurement

Secondary Outcomes (16)

• Difference between "break points" for alcohol on 1st alcohol self-administration (ASA) day and 2nd ASA day

  18 to 31 day between 1st and 2nd measurement

• Difference between max. achieved blood alcohol concentrations (BAC) on 1st alcohol self-administration (ASA) day and 2nd ASA day

  18 to 31 day between 1st and 2nd measurement

• Difference between cumulative CAT trials for sodium chloride on 1st alcohol self-administration (ASA) day and 2nd ASA day.

  18 to 31 days between 1st and 2nd measurement

• Differences in 1st and 2nd half of self-administration periods between cumulative CAT trials for alcohol on 1st alcohol self-administration (ASA) day and 2nd ASA day of 1st and 2nd half of self-administration periods.

  18 to 31 days between 1st and 2nd measurement

• Differences in 1st and 2nd half of self-administration periods between "break points" for alcohol on 1st alcohol self-administration (ASA) day and 2nd ASA day.

  18 to 31 days between 1st and 2nd measurement

Other Outcomes (2)

• CIWA-Ar-Score

  39 - 90 days between screening and visit 6, 32 - 55 days between visit 1 and visit 6

• adverse events / serious adverse events

  32 - 55 days between visit 1 and visit 6

Study Arms (3)

Acamprosate

ACTIVE COMPARATOR

1 capsule with Acamprosate calcium * oral use * 3 times / day (morning, noon, evening) * 666 mg per capsule * 14 - 19 days

Drug: Acamprosate Calcium; Drug: Placebo lead in

Calcium Carbonate

ACTIVE COMPARATOR

1 capsule with Calcium Carbonate * oral use * 3 times / day (morning, noon, evening) * 1500 mg Calcium Carbonate (= 600 mg Calcium 2+) * 14 - 19 days

Drug: Calcium Carbonate; Drug: Placebo lead in

Placebo

PLACEBO COMPARATOR

1 capsule placebo, * oral use * 3 times / day (morning, noon, evening) * 14 - 19 days

Drug: Placebo; Drug: Placebo lead in

Interventions

Acamprosate Calcium DRUG

1 capsule with 666 mg Acamprosate

Also known as: Campral

Acamprosate

Calcium Carbonate DRUG

1 capsule with 1500 mg Calcium Carbonate

Also known as: Calcium

Calcium Carbonate

Placebo DRUG

1 Capsule with Placebo (lactose monohydrate, micro crystalline cellulose, magnesium stearate)

Placebo

Placebo lead in DRUG

1 Capsule with Placebo (lactose monohydrate, micro crystalline cellulose, magnesium stearate)

Acamprosate; Calcium Carbonate; Placebo

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• male and female volunteers aged 25 to 55 years, who meet or met the diagnostic criteria of an at least mild alcohol use disorder (DSM-5), but do not want to cease alcohol consumption
• willingness to stop alcohol and drug consumption for 15-20 days for the purpose of study participation
• at least high risky alcohol drinkers (WHO) in the Timeline Follow-back Interview over the last 45 day with an average amount of alcohol of 60 g/day (men) or 40 g/day (women) with at least 4 drinking days per week
• informed consent
• ability to swallow a placebo capsule
• not more than 6 consecutive alcohol abstinent days between screening and visit 2

You may not qualify if:

• Current Substance dependence (illegal drugs) ICD-10 or DSM-IV
• Intention to stop alcohol consumption immediately and permanently
• Current or previous disease that could cause a clinically relevant hazard (e.g. pancreatitis, cirrhosis)
• kidney stone disease
• Current Treatment with psychotropic drugs or current psychiatric disorder in need of treatment
• alcohol withdrawal symptoms (at Screening, visit 1 or visit 2) with CIWA-Ar-Score \> 6 points or arterial blood pressure \>160 mm Hg or diastolic blood pressure \> 100 mm Hg or heart rate \>105 bpm (when breath alcohol concentration 0 mg%)
• history of epileptic seizure or delirium
• routine laboratory parameters, indicating relevant liver-, pancreas- or kidney injury, an acute infection, anemia or lack of vitamins (ASAT, ALAT, lipase \> threefold of the standard at screening, Quick's value \< 70%, creatinine \> 120 µmol/l, eGFR \< 30 mol/min/1.73 m², leucocytes \> 13000/µl, haemoglobin \< 7.5 mmol/l (men) or 6.5 mmol/l (women), MCV \> 105 fl, calcium level at screening \> 2.7 mmol/l
• body weight \> 120 kg (Screening)
• Breath alcohol concentration at screening or visit 1 or visit 2 two times \> 0 mg% or drug screening two times positive for opiate, cannabis, cocaine, amphetamine, benzodiazepine
• history of hypersensitivity to alcohol or one of the used medicinal products, of their ingredients or medicinal products with similar chemical structures
• history of inefficient treatment with Acamprosate
• disorders, which will not allow the subject to assess the character and importance or possible consequences of the clinical trial
• pregnant or breastfeeding women
• women capable of bearing children, except women who fulfil following criteria:- post-menopausal (12 months natural amenorrhoea or 6 month amenorrhoea and Serum FSH \>40 ml U/ml) - post operative (6 weeks after ovariectomy on both sides with or without hysterectomy) - regular and correct use of a contraceptive method with an error Quote of \< 1 % per year (for example implants, depot injections, oral contraceptive, IUP). It has to be recognized that a combined oral contraception - in contrast to pure progesterone compounds - have a failure rate of \< 1 %. Hormone IUDs with a Pearl Index of 1 % are safer than copper IUDs. - sexual abstinence - vasectomy of the Partner)

Sponsors & Collaborators

• Technische Universität Dresden: lead

Study Sites (1)

Klinik und Poliklinik für Psychiatrie und Psychotherapie; Technische Universität Dresden

Dresden, Saxony, 01307, Germany

Location

MeSH Terms

Conditions

Alcoholism

Interventions

Acamprosate; Calcium Carbonate; Calcium

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Taurine; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Calcium Compounds; Inorganic Chemicals; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Minerals; Metals, Alkaline Earth; Elements; Metals; Blood Coagulation Factors; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2018
• First Posted: August 17, 2018
• Study Start: August 5, 2020
• Primary Completion: August 30, 2023
• Study Completion: May 1, 2024
• Last Updated: May 29, 2024

Record last verified: 2024-05

Locations

DE (1)